Neuroanatomical determinants of the sympathetic nerve responses evoked by leptin

Abstract

Leptin is an adipocyte-derived hormone that relays a satiety signal to the brain. The effect of leptin on the sympathetic nervous system is an important aspect in the regulation of energy homeostasis as well as several other physiological functions. The arcuate nucleus of the hypothalamus is considered a major site for the regulation of physiological processes by leptin. However, there is growing recognition that other hypothalamic and extra-hypothalamic brain nuclei are important for leptin regulation of physiological processes including sympathetic nerve traffic. The current review discusses the various hypothalamic and extra-hypothalamic nuclei that have been implicated in leptin-induced increase in regional sympathetic nerve activity. The continuous rise in the prevalence of obesity underscores the importance of understanding the underlying neural mechanisms regulating sympathetic traffic to different tissues to design effective strategies to reverse obesity and associated diseases.

Fig. 1

Several physiological processes are influenced by leptin through activation of the sympathetic nervous system. Leptin action in the brain triggers an increase in sympathetic nerve outflow to a variety of tissues involved in several physiological functions ranging from energy expenditure and metabolism to cardiovascular control. BAT brown adipose tissue, WAT white adipose tissue, Ske Mus skeletal muscle, Adrenal gl adrenal gland

Fig. 2

Schematic illustration of the various brain nuclei in which leptin receptor signaling has been shown to elicit an increase in sympathetic nerve activity. The insert shows the two neuronal populations within the arcuate nucleus and their projections to the second order neurons. In POMC neurons, leptin increases neuronal firing and POMC gene expression promoting the secretion of alpha-melanocyte stimulating hormone (α-MSH), an agonist of the melanocortin 3 and 4 receptors (MC3/4R) located in the second order neurons. Conversely, in NPY neurons, leptin inhibit neuronal firing rate and decrease the expression and secretion of AgRP (antagonist of the MC3/4R), promoting MC3/4R activation